Rubella is a highly contagious
viral infection that usually causes a mild disease in children and adults. However,
infection during pregnancy can result in a fetal or newborn death or
congenital rubella syndrome (
CRS), a constellation of permanent
birth defects including
cataracts, heart defects, and sensorineural
deafness. The live-attenuated
rubella vaccine has been highly effective, with the Americas declared free of endemic
rubella transmission in 2015. However,
rubella remains a significant problem worldwide and the leading cause of
vaccine-preventable
birth defects globally. Thus, elimination of
rubella and CRS is a goal of the World Health Organization. No specific
therapeutics are approved for the rubella virus. Therefore, we set out to identify whether existing small molecules may be repurposed for use against rubella virus
infection. Thus, we performed a high-throughput screen for small molecules active against rubella virus in human respiratory cells and identified two
nucleoside analogs, NM107 and
AT-527, with potent
antiviral activity. Furthermore, we found that combining these
nucleoside analogs with inhibitors of host
nucleoside biosynthesis had synergistic
antiviral activity. These studies open the door to new potential approaches to treat
rubella infections.